Abstract
In the light of the recent accumulated knowledge on SARS-CoV-2 and its mode of human cells invasion, the binding of viral spike glycoprotein to human Angiotensin Converting Enzyme 2 (hACE2) receptor plays a central role in cell entry. We designed a series of peptides mimicking the N-terminal helix of hACE2 protein which contains most of the contacting residues at the binding site and have a high helical folding propensity in aqueous solution. Our best peptide mimics bind to the virus spike protein with high affinity and are able to block SARS-CoV-2 human pulmonary cell infection with an inhibitory concentration (IC50) in the nanomolar range. These first in class blocking peptide mimics represent powerful tools that might be used in prophylactic and therapeutic approaches to fight the coronavirus disease 2019 (COVID-19).
Competing Interest Statement
The authors declare the following competing financial interest(s): The patent application EP20305449.9 included results from this paper. The authors declare that no other competing interests exist.
Footnotes
Philippe Karoyan dedicates this work to Gérard Chassaing on the occasion of his 75th birthday. “There are no borders in science. The only limit is our imagination.”
In Brief Helical peptides mimicking H1 helix of hACE2 and composed of only natural amino acids bind to SARS-CoV-2 spike protein with high affinity and block human pulmonary cells infection with IC50 in the nM range.
Highlights Peptide mimics of hACE2 designed from H1 helix and composed of only natural amino acids show high helical folding propensity in aqueous media. These peptide mimics bind to virus spike RBD with high affinity (sub-nM range). These peptide mimics block SARS-CoV-2 pulmonary cells infection with an IC50 in the nM range. These peptide mimics are devoid of toxicity on pulmonary cells.